The background description provided herein is for the purpose of generally presenting the context of the invention. The subject matter discussed in the background of the invention section should not be assumed to be prior art merely as a result of its mention in the background of the invention section. Similarly, a problem mentioned in the background of the invention section or associated with the subject matter of the background of the invention section should not be assumed to have been previously recognized in the prior art. The subject matter in the background of the invention section merely represents different approaches, which in and of themselves may also be inventions. Work of the presently named inventors, to the extent it is described in the background of the invention section, as well as aspects of the description that may not otherwise qualify as prior art at the time of filing, are neither expressly nor impliedly admitted as prior art against the invention.
Dialysis is the chemical process by which particles in a liquid, such as organic or inorganic molecules of various sizes and properties, are separated based upon differences in their ability to pass through the pores of a semipermeable membrane. In medicine, dialysis refers to the clinical purification of blood by allowing excess water, urea, and other waste molecules in the blood to cross, by passive diffusion, down a concentration gradient and across the semipermeable membrane, from a region of high concentration (the blood) to a solution of pure water, electrolytes, and salts, termed the dialysate. Within the dialysis system, dialysate delivered to the membrane has a low concentration of the waste products and, if excess water is to be removed from the blood, a higher osmolarity to support the diffusion of water across the membrane into the dialysate. As the concentration of the chemical species to be dialyzed increases within the dialysate contained by the membrane, that dialysate is replaced with fresh dialysate so that dialysis can proceed unimpeded.
In the case of kidney dialysis as a substitute for the normal function of the kidney, the purpose of the dialysate is to pull toxins and excess water from the blood into the dialysate by diffusion down a concentration gradient that is supported by a semi-permeable membrane that, if desired, can be impermeable to large molecules in blood such as albumin.
Microdialysis is a functionally equivalent process using a small cylindrical probe with a semipermeable membrane at its end to collect for analysis specific chemicals released by cells in a small region of the intact brain, for example, or cells being cultured in a Petri dish. There is a substantial body of literature on microdialysis of the brain [6, 44]. An excellent example of in vitro microdialysis is provided by MacVane et al. [27]. Brain microdialysis works through diffusing molecules through a semipermeable membrane which is located at the tip of the probe. There are two modes associated with the process, dialysis where molecules are removed from the system for analysis, and retrodialysis where molecules such as a drug are delivered to the biological system under study. Both modes are a result of diffusion that causes molecules to be transported from the inside of the tip into the brain microenvironment and other to molecules in the brain microenvironment to be transported by diffusion to the inside of the tip.
In addition to the microdialysis as described above, there are a wide variety of other methods to perform the collection and analysis of the chemicals associated with a living or fixed biological sample such as the cells. Imaging mass spectrometry (matrix assisted laser desorption ionization (MALDI MS)) places the fixed or frozen samples in vacuum and uses a scanning laser to ionize chemical species in the matrix-coated sample [2, 3, 31]. There is a growing literature on air-sampling mass spectrometry, e.g., desorption electrospray ionization (DESI) and liquid junction mass spectrometry and other related techniques [3, 5, 7-9, 13-23, 25, 26, 29-43].
All of these air-sampling approaches utilize a single point collection probe that is placed adjacent to a horizontal or vertical sample. The delivery probe may deliver solvent, ionized gas, deionized water or other liquids, desorption matrix, and/or laser light to the sample, or may not be required for a particular analysis approach. It is also possible to utilize acoustic loading to deliver a sample of fluid from a well plate or dish directly to a mass spectrometer [36].
When trying to determine the spatiotemporal nature of gene-regulatory and metabolic signaling and control networks, the aforementioned point-sampling approaches have a significant disadvantage: while the collection probe is gathering analyte from a particular location for subsequent analysis, the adjacent locations are biologically active and are both consuming and releasing chemicals to support their metabolic and signaling activities, which, in the case of heterogeneous tissues of common interest, may have a substantially different temporal composition profile than the adjacent region being sampled at that time.
For low concentration signals, the analyte not being detected is lost by diffusive or advective mixing into the bulk media surrounding the sample while analyte is being detected at another location. In addition, the ability to sample only one location at a time provides an incomplete description of the chemical activity at that region that has occurred since the previous time it was sampled. The signal at one location is not being integrated over time, and there is a risk of under-sampling of the concentration time profile with the concomitant risk of violating the Shannon/Nyquist sampling theorem and producing temporally aliased concentration profiles.
Therefore, a heretofore unaddressed need exists in the art to address the aforementioned deficiencies and inadequacies.